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The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral cDNA

  1. Author:
    Keating, C. P.
    Hill, M. K.
    Hawkes, D. J.
    Smyth, R. P.
    Isel, C.
    Le, S. Y.
    Palmenberg, A. C.
    Marshall, J. A.
    Marquet, R.
    Nabel, G. J.
    Mak, J.

  2. Author Address

    Keating, Cameron P.; Hill, Melissa K.; Hawkes, David J.; Smyth, Redmond P.; Mak, Johnson] Macfarlane Burnet Inst Med Res & Publ Hlth, Ctr Virol, Melbourne, Vic, Australia. [Hawkes, David J.; Smyth, Redmond P.; Mak, Johnson] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia. [Hill, Melissa K.; Mak, Johnson] Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia. [Isel, Catherine, Marquet, Roland] Univ Strasbourg, CNRS, IBMC, Architecture & Reactivite ARN, Strasbourg, France. [Le, Shu-Yun] NCI, Ctr Canc Res Nanobiol Program, CCR, Frederick, MD 21701 USA. [Palmenberg, Ann C.] Univ Wisconsin, Inst Mol Virol, Madison, WI 53706 USA. [Marshall, John A.] VIDRL, Melbourne, Vic, Australia. [Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
    1. Year: 2009
  2. Journal: Nucleic Acids Research
    1. 37
    2. 3
    3. Pages: 945-956
  4. Type of Article: Proceedings Paper
  1. Abstract:

    The bias of A-rich codons in HIV-1 pol is thought to be a record of hypermutations in viral genomes that lack biological functions. Bioinformatic analysis predicted that A-rich sequences are generally associated with minimal local RNA structures. Using codon modifications to reduce the amount of A-rich sequences within HIV-1 genomes, we have reduced the flexibility of RNA sequences in pol to analyze the functional significance of these A-rich 'structurally poor' RNA elements in HIV-1 pol. Our data showed that codon modification of HIV-1 sequences led to a suppression of virus infectivity by 5-100-fold, and this defect does not correlate with, viral entry, viral protein expression levels, viral protein profiles or virion packaging of genomic RNA. Codon modification of HIV-1 pol correlated with an enhanced dimer stability of the viral RNA genome, which was associated with a reduction of viral cDNA synthesis both during HIV-1 infection and in a cell free reverse transcription assay. Our data provided direct evidence that the HIV-1 A-rich pol sequence is not merely an evolutionary artifact of enzyme-induced hypermutations, and that HIV-1 has adapted to rely on A-rich RNA sequences to support the synthesis of viral cDNA during reverse transcription, highlighting the utility of using structurally poor' RNA domains in regulating biological process.

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External Sources

  1. PMID: 19106143

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